A Study to Investigate the Effect of Mild and Moderate Hepatic Impairment on the Safety and Tolerability of Fezolinetant Compared to Participants With Normal Hepatic Function

NCT04482270 | Completed Phase 1 FDA Drug

• 1 other identifier: 2693-CL-0007
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 4

Brief Summary

The purpose of this study is to evaluate the pharmacokinetics of a single oral dose of fezolinetant and ES259564 (fezolinetant metabolite) in female participants with mild and moderate hepatic impairment compared to healthy female participants with normal hepatic function. This study will also evaluate the safety and tolerability of a single oral dose of fezolinetant in female participants with mild and moderate hepatic impairment and healthy female participants with normal hepatic function.

Conditions

Hepatic Impairment; Healthy Volunteers

Keywords

ES259564; Pharmacokinetics; fezolinetant; Healthy Volunteers; Hepatic Impairment

Outcome Measures

Primary Outcomes (8)

• Pharmacokinetics (PK) of Fezolinetant in Plasma: Area Under the Concentration-time Curve (AUC) From the Time of Dosing Extrapolated to Time Infinity (AUCinf)

  AUCinf will be recorded from the PK plasma samples collected.

  Up to 5 days

• PK of Fezolinetant in Plasma: AUC From the Time of Dosing to the Last Measurable Concentration (AUClast)

  AUClast will be recorded from the PK plasma samples collected.

  Up to 5 days

• PK of Fezolinetant in Plasma: Maximum Concentration (Cmax)

  Cmax will be recorded from the PK plasma samples collected.

  Up to 5 days

• PK of Fezolinetant in Plasma: Apparent Clearance (CL/F)

  CL/F will be recorded from the PK plasma samples collected.

  Up to 5 days

• PK of Fezolinetant in Plasma: Apparent volume of Distribution During Terminal Phase After Non-intravenous Administration (Vz/F)

  Vz/F will be recorded from the PK plasma samples collected.

  Up to 5 days

• PK of Fezolinetant Metabolite ES259564 in Plasma: AUCinf

  AUCinf will be recorded from the PK plasma samples collected.

  Up to 5 days

• PK of Fezolinetant Metabolite ES259564 in Plasma: AUClast

  AUClast will be recorded from the PK plasma samples collected.

  Up to 5 days

• PK of Fezolinetant Metabolite ES259564 in Plasma: Cmax

  Cmax will be recorded from the PK plasma samples collected.

  Up to 5 days

Secondary Outcomes (4)

• Number of Participants With Adverse Events (AEs)

  Up to 14 days

• Number of Participants With Laboratory Value Abnormalities and/or Adverse Events (AEs)

  Up to 14 days

• Number of Participants With Vital Sign Abnormalities and/or Adverse Events (AEs)

  Up to 14 days

• Number of Participants With 12-lead Electrocardiogram (ECG) Abnormalities and/or Adverse Events (AEs)

  Up to 14 days

Study Arms (3)

Fezolinetant: Mild Hepatic Impairment

EXPERIMENTAL

Participants will receive a single oral dose of fezolinetant under fasting conditions on Day 1.

Drug: fezolinetant

Fezolinetant: Moderate Hepatic Impairment

EXPERIMENTAL

Participants will receive a single oral dose of fezolinetant under fasting conditions on Day 1.

Drug: fezolinetant

Fezolinetant: Normal Hepatic Function

EXPERIMENTAL

Participants will receive a single oral dose of fezolinetant under fasting conditions on Day 1.

Drug: fezolinetant

Interventions

fezolinetant DRUG

Oral

Also known as: ESN364

Fezolinetant: Mild Hepatic Impairment; Fezolinetant: Moderate Hepatic Impairment; Fezolinetant: Normal Hepatic Function

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject has a Body Mass Index (BMI) range of 18.5 to 36.0 kg/m\^2, inclusive and weighs at least 50 kg at screening.
• Female subject is not pregnant and at least one of the following conditions apply:
• Not a woman of childbearing potential (WOCBP)
• WOCBP who agrees to follow the contraceptive guidance for at least 30 days prior to day -1 through at least 30 days after IP administration.
• Female subject must agree not to breastfeed starting at screening and throughout the study period and for 30 days after IP administration.
• Female subject must not donate ova starting at first dose of IP and throughout the study period and for 30 days after IP administration.
• Subject agrees not to participate in another interventional study while participating in the present study.
• Additional Criterion for Subjects with Hepatic Impairment:
• Subject has mild (Child-Pugh classification Class A, score 5 or 6) or moderate (Child-Pugh classification Class B, score 7 to 9) hepatic impairment.

You may not qualify if:

• Subject has received any investigational therapy within 28 days or five half-lives, whichever is longer, prior to Day -1.
• Subject has any condition which makes the subject unsuitable for study participation.
• Female subject who has been pregnant within six months prior to screening or breastfeeding within three months prior to screening.
• Subject has a known or suspected hypersensitivity to fezolinetant or any components of the formulation used.
• Subject has had previous exposure with fezolinetant.
• Subject has used any inducer of cytochrome P450 (CYP) 1A2 in the three months prior or inhibitors of CYP 1A2 in the two weeks or five half-lives of the inhibitor, whichever is longer, prior to Day -1.
• Subject has any clinically significant history of allergic conditions (including drug allergies, asthma, eczema or anaphylactic reactions, but excluding untreated, asymptomatic, seasonal allergies) prior to IP administration.
• Subject has/had febrile illness or symptomatic, viral (excluding chronic hepatitis B and C), bacterial (including upper respiratory infection) or fungal (noncutaneous) infection within one week prior to Day -1.
• Subject has smoked, used tobacco-containing products and nicotine or nicotine-containing products (e.g., electronic vapes) within six months prior to screening or the subject tests positive for cotinine at screening or on Day -1.
• Subject has had significant blood loss, donated ≥ 1 unit (450 mL) of whole blood or donated plasma within seven days prior to Day -1 and/or received a transfusion of any blood or blood products within 60 days.
• Subject is an employee of Astellas, the study-related contract research organizations (CROs) or the clinical unit.
• Subject has creatinine level outside normal limits on Day -1. In such a case, the assessment may be repeated once.
• Additional Criteria for Subjects with Hepatic Impairment:
• Subject has any history or evidence of any clinically significant cardiovascular, gastrointestinal, endocrinologic, hematologic, immunologic, metabolic, dermatologic, psychiatric, renal and/or other major disease or malignancy, not related to current disease state.
• Subject has a history of consuming \> 7 units of alcoholic beverages per week within three months prior to screening or has a history of alcoholism or drug/chemical/substance abuse within one year prior to screening (note: 1 unit = 12 ounces of beer, 4 ounces of wine, 1 ounce of spirits/hard liquor) or the subject tests positive for alcohol at screening or on Day -1.

Sponsors & Collaborators

• Astellas Pharma Global Development, Inc.: lead

Study Sites (4)

Clinical Research of West Florida, Inc.

Clearwater, Florida, 33765, United States

Location

Clinical Pharmacology of Miami, LLC

Miami, Florida, 33014-361, United States

Location

Orlando Clinical Research Center

Orlando, Florida, 32809, United States

Location

American Research Corporation

San Antonio, Texas, 72815, United States

Location

MeSH Terms

Interventions

fezolinetant

Study Officials

• Executive Medical Director

  Astellas Pharma Global Development, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 20, 2020
• First Posted: July 22, 2020
• Study Start: September 2, 2020
• Primary Completion: March 22, 2021
• Study Completion: March 22, 2021
• Last Updated: October 17, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)